ES2965754T3 - 2-Iminobiotina para uso en el tratamiento de lesiones de células cerebrales - Google Patents

2-Iminobiotina para uso en el tratamiento de lesiones de células cerebrales Download PDF

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Publication number: ES2965754T3
Authority: ES; Spain
Prior art keywords: iminobiotin; individual; day; administered; dose
Prior art date: 2015-12-16
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

ES16825913T

Other languages

English (en)

Spanish (es)

Inventor

Paul Willem Theresia Josef Leufkens

Cacha Marie Pétronelle Cathérine Dorothée Peeters

Huibert Alexander Tjabbes

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Neurophyxia BV

Original Assignee

Neurophyxia BV

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2015-12-16

Filing date

2016-12-16

Publication date

2024-04-16

2016-12-16 Application filed by Neurophyxia BV filed Critical Neurophyxia BV

2024-04-16 Application granted granted Critical

2024-04-16 Publication of ES2965754T3 publication Critical patent/ES2965754T3/es

Status Active legal-status Critical Current

2036-12-16 Anticipated expiration legal-status Critical

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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere

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ES16825913T 2015-12-16 2016-12-16 2-Iminobiotina para uso en el tratamiento de lesiones de células cerebrales Active ES2965754T3 (es)

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US (3)	US10525039B2 (pl)
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AU (1)	AU2016372396B2 (pl)
CA (1)	CA3008790A1 (pl)
DK (1)	DK3389653T3 (pl)
ES (1)	ES2965754T3 (pl)
FI (1)	FI3389653T3 (pl)
PL (1)	PL3389653T3 (pl)
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US10525039B2 (en)	2015-12-16	2020-01-07	Neurophyxia B.V.	2-iminobiotin for use in the treatment of brain cell injury
US11998001B2 (en) *	2018-02-09	2024-06-04	Yale University	Perfusion device for normothermic, ex vivo preservation of a mammalian brain
US20240173301A1 (en) *	2021-03-23	2024-05-30	Neurophyxia B.V.	2-iminobiotin for use in the treatment of stroke
WO2022203505A1 (en) *	2021-03-23	2022-09-29	Neurophyxia B.V.	2-iminobiotin for use in the treatment of stroke

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AU772204B2 (en)	1999-01-21	2004-04-22	Bristol-Myers Squibb Company	Complex of ras-farnesyltransferase inhibitor and sulfobutylether-7-beta-cyclodextrin or 2-hydroxypropyl-beta-cyclodextrin and method
US7087633B2 (en)	2000-03-31	2006-08-08	Universitair Medisch Centrum	Method for treating perinatal asphyxia in a human or animal neonate
WO2001074351A1 (en)	2000-03-31	2001-10-11	Universitair Medisch Centrum	Composition for the prevention and/or treatment, in newborn babies, of the effects of complications during childbirth
US7319090B2 (en)	2002-11-27	2008-01-15	University Of North Carolina At Chapel Hill	Methods of treating cerebral ischemia
US20090197966A1 (en)	2006-10-04	2009-08-06	Uno Jakob Weber	Use of Hypothermia Inducing Drugs
MX338405B (es)	2010-05-26	2016-04-14	Neurophyxia B V	Formulaciones de 2-iminobiotina y sus usos.
AU2013264820A1 (en) *	2012-05-23	2014-11-27	Cellixbio Private Limited	Compositions and methods for treatment of mucositis
GB2504263B (en)	2012-06-08	2015-09-16	Gw Pharma Ltd	Synergistic therapies for neuroprotection
US10092591B2 (en) *	2014-02-27	2018-10-09	University Of Alaska Fairbanks	Methods and compositions for the treatment of ischemic injury to tissue using therapeutic hypothermia
US10525039B2 (en)	2015-12-16	2020-01-07	Neurophyxia B.V.	2-iminobiotin for use in the treatment of brain cell injury

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US10722496B2 (en)	2020-07-28
US11426387B2 (en)	2022-08-30
AU2016372396A1 (en)	2018-06-28
JP2019501969A (ja)	2019-01-24
FI3389653T3 (fi)	2023-12-18
US20200338046A1 (en)	2020-10-29
US10525039B2 (en)	2020-01-07
WO2017105237A1 (en)	2017-06-22
AU2016372396B2 (en)	2022-04-14
PT3389653T (pt)	2023-12-28
PL3389653T3 (pl)	2024-02-26
CA3008790A1 (en)	2017-06-22
EP3389653A1 (en)	2018-10-24
JP6975165B2 (ja)	2021-12-01
EP3389653B1 (en)	2023-11-08
US20200147049A1 (en)	2020-05-14
DK3389653T3 (da)	2024-01-02
US20190262316A1 (en)	2019-08-29

Publication	Publication Date	Title
US11426387B2 (en)	2022-08-30	2-iminobiotin for use in the treatment of brain cell injury
ES2307975T3 (es)	2008-12-01	Composiciones analgesicas que comprenden antagonistas del receptor de nmda y cloruro de benzalconio.
ES2294543T3 (es)	2008-04-01	Uso de sales de nitrilo para el tratamiento de afecciones cardiovasculares.
Sifringer et al.	2015	Neuroprotective effect of dexmedetomidine on hyperoxia‐induced toxicity in the neonatal rat brain
Shadman et al.	2019	Magnesium sulfate protects blood–brain barrier integrity and reduces brain edema after acute ischemic stroke in rats
Zou et al.	2015	Electroacupuncture pretreatment attenuates blood‑brain barrier disruption following cerebral ischemia/reperfusion
ES3062284T3 (en)	2026-04-09	Compositions for use in treating psychotic disorders
ES2327286T3 (es)	2009-10-27	Formulacion liquida de paracetamol inyectable.
Han et al.	2020	GYY4137 protects against MCAO via p38 MAPK mediated anti-apoptotic signaling pathways in rats
Milani et al.	2016	The R18 polyarginine peptide is more effective than the TAT‐NR2B9c (NA‐1) peptide when administered 60 minutes after permanent middle cerebral artery occlusion in the rat
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McCully et al.	2003	Mitochondrial ATP-sensitive potassium channels in surgical cardioprotection
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RU2431496C2 (ru)	2011-10-20	Инъекционная лекарственная форма для лечения острого ишемического инсульта и черепно-мозговой травмы, способ ее изготовления и применение
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WO2017190713A1 (es)	2017-11-09	Derivado de benzodiazepina con actividad sobre el sistema nervioso central y vascular
ES2277567B1 (es)	2008-06-01	Compuestos con propiedades neuroprotectoras.
ES2410230B1 (es)	2014-04-04	Composición farmacéutica para el tratamiento de las enfermedades cerebrovasculares.
ES2326355B1 (es)	2010-08-10	Acido 1-(di-n-propilacetilaminometil)-ciclohexilacetico.
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